健脾养正消癥方对脾胃虚弱型中晚期胃癌化疗患者肠道菌群的影响

Effects of decoction for fortifying spleen,nourishing health Qi and removing mass on the intestinal flora in patients with advanced gastric cancer of type of spleen and stomach deficiency undergoing chemotherapy

目的基于肠道微生态学探讨健脾养正消癥方辅助胃癌化疗可能的机制。方法将2021年1—12月于江苏省中医院住院治疗的46例脾胃虚弱型中晚期胃癌患者随机分为对照组23例和试验组23例,另以同期健康志愿者30例作为健康组。对照组患者给予以奥沙利铂联合氟尿嘧啶类为基础的化疗方案治疗,试验组患者在化疗(方案同对照组)基础上给予健脾养正消癥方加减口服,2组均完成2个化疗周期治疗。比较2组患者治疗前后KPS评分、中医证候积分及治疗后胃肠道不良反应发生情况;采集2组患者治疗前后和30例健康人的粪便样本,利用16SrDNA测序技术分析肠道菌群物种结构、相对丰度。结果试验组患者治疗后KPS评分明显高于治疗前及对照组(P均<0.05),中医证候积分明显低于治疗前及对照组(P均<0.05),对照组患者治疗前后KPS评分及中医证候积分比较差异均无统计学意义(P均>0.05)。试验组患者治疗后腹泻的发生率明显低于对照组(P<0.05)。3组Shannon指数比较差异均无统计学意义(P均>0.05)。2组患者治疗前后Chao指数均明显高于健康组(P均<0.05),但试验组患者治疗后Chao指数明显低于对照组(P<0.05),试验组患者治疗后菌群物种结构较对照组更接近健康组。2组患者治疗前梭杆菌门、脱硫弧菌属、梭杆菌属及颤螺旋菌科UCG_002属的相对丰度均明显高于健康组(P均<0.05),霍氏真杆菌属明显低于健康组(P均<0.05)。对照组患者治疗后霍氏真杆菌属相对丰度明显下降(P<0.05),颤螺旋菌科UCG_002属相对丰度明显上升(P<0.05);试验组患者治疗后霍氏真杆菌属相对丰度明显上升(P<0.05),梭杆菌门、梭杆菌属相对丰度明显下降(P均<0.05),颤螺旋菌科UCG_002属相对丰度治疗前后比较差异无统计学意义(P>0.05)。结论健脾养正消癥方可能通过调节肠道菌群的丰富度,逆转化疗导致的部分肠道菌群变化,增加有益菌,减少条件致病菌,从而发挥辅助脾胃虚弱型中晚期胃癌化疗的作用。

Objective It is to explore the possible mechanisms of decoction for fortifying spleen,nourishing health Qi and removing mass in the assist chemotherapy for gastric cancer based on intestinal microecology.Methods Forty-six patients with advanced gastric cancer of type of spleen and stomach deficiency were randomly divided into control group(23 cases)and experimental group(23 cases),another 30 cases of healthy volunteers in the same period were used as the healthy group.The patients in the control group were given chemotherapy based on oxaliplatin combined with fluorouracil,while the patients in the experimental group were orally given decoction for fortifying spleen,nourishing health Qi and removing mass on the basis of chemotherapy(same as that of the control group),and the two groups both completed 2 cycles of chemotherapy.The KPS scores,TCM syndrome scores of the patients before and after treatment and the occurrence of gastrointestinal adverse reactions after treatment were compared between the two groups;the fecal samples from the patients of the two groups before and after treatment and from 30 healthy volunteers were collected to analyze the species structure and relative abundance of the intestinal flora by 16SrDNA sequencing technology.Results After treatment,the KPS scores of the patients in the experiment group was significantly higher than that before treatment and in the control groups(all P<0.05),and the TCM syndrome scores were significantly lower than that before treatment and in the control groups(all P<0.05),there was no significant changes in the KPS scores and TCM syndrome of the patients in the control group(all P>0.05).The incidence of post-treatment diarrhea of patients in the experiment group was significantly lower than that in the control group(P<0.05).The differences in the Shannon indexes were not statistically significant among the three groups(all P>0.05).The Chao indexes of the patients in the two groups before and after treatment were significantly higher than that in the healthy group(all P<0.05),but the Chao indexe of the patients in the experiment group was significantly lower than that in the control group after treatment(P<0.05),the species structure of the bacterial flora of patients in the experimental group was more closer to that in the healthy group compared with the control group after treatment.Before treatment,the relative abundances of Fusobacteriota,Desulfovibrio,Fusobacterium,Oscillospiraceae_UCG_002 of patients in the two groups were significantly higher than those in the healthy group(all P<0.05),and those of Eubacterium_hallii_group were significantly lower than that in the healthy group(P<0.05).After treatment,the relative abundance of Eubacterium_hallii_group in the control group was significantly decreased(P<0.05),and the relative abundance of Oscillospiraceae_UCG_002 was significantly increased(P<0.05).After treatment,the relative abundance of Eubacterium_hallii_group in the experimental group was significantly increased(P<0.05),while the relative abundances of Fusobacteriota and Fusobacterium were significantly decreased(P<0.05),and there was no statistical difference in the relative abundance of Oscillospiraceae_UCG_002 between before and after treatment(P>0.05).Conclusion Decoction for fortifying spleen,nourishing health Qi and removing mass may play its role in the assist chemotherapy for gastric cancer by regulating the richness of intestinal flora,reversing some intestinal bacterial changes caused by chemotherapy,increasing beneficial bacteria,and reducing opportunistic pathogenic bacteria.